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Regulation of bone homeostasis by controlling osteoclasts and osteoblasts

Research Project

Project/Area Number 24390359
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionKeio University

Principal Investigator

MIYAMOTO Takeshi  慶應義塾大学, 医学部, 講師 (70383768)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2012: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Keywords骨代謝 / 破骨細胞 / 骨芽細胞 / 骨粗鬆症 / Blimpl / 分化 / 骨
Outline of Final Research Achievements

Bone homeostasis is regulated in a delicate balance between bone resorbing osteoclasts and bone forming osteoblasts. In this study, we found that B lymphocyte induced maturation protein 1 (Blimp1) plays a crucial role in regulating osteoclastogenesis and bone mass at an adult stage, and targeting Blimp1 in adult mice resulted in significant inhibition of osteoclast formation followed by increased bone mass. We also found that osteoclast stimulatory transmembrane protein (OC-STAMP) is required for osteoclast cell-cell fusion, and OC-STAMP-deficient mice exhibited complete abrogation of osteoclast cell-cell fusion. We further found that B cell lymphoma 6 (Bcl6) plays a role in regulating osteoblastogenesis via suppressing expression of signal transducer and activator of transcription 1 (Stat1), and Bcl6-deificient osteoblasts showed altered differentiation owing to Stat1 elevation. Bcl6/Stat1 doubly deficient mice exhibited reversed osteoblastogenesis compared with Bcl6-deficient mice.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (38 results)

All 2015 2014 2013 2012

All Journal Article (18 results) (of which Peer Reviewed: 18 results,  Acknowledgement Compliant: 4 results) Presentation (20 results) (of which Invited: 6 results)

  • [Journal Article] Interleukin-1 receptor-associated kinase-4 (IRAK4) promotes inflammatory osteolysis by activating osteoclasts and inhibiting formation of foreign body giant cells.2015

    • Author(s)
      Katsuyama E, Miyamoto H, Kobayashi T, Sato Y, Hao W, Kanagawa H, Fujie A, Tando T, Watanabe R, Morita M, Miyamoto K, Niki Y, Morioka H, Matsumoto M, Toyama Y, Miyamoto T.
    • Journal Title

      J Biol Chem.

      Volume: 290 Issue: 2 Pages: 716-726

    • DOI

      10.1074/jbc.m114.568360

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mycobacterium tuberculosis promotes arthritis development through toll-like receptor 2.2015

    • Author(s)
      Kanagawa H, Niki Y, Kobayashi T, Sato Y, Katsuyama E, Fujie A, Hao W, Miyamoto K, Tando T, Watanabe R, Morita M, Morioka H, Matsumoto M, Toyama Y, Miyamoto T.
    • Journal Title

      J Bone Miner Metab.

      Volume: 33 Issue: 2 Pages: 135-141

    • DOI

      10.1007/s00774-014-0575-9

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Bcl6 promotes osteoblastogenesis through Stat1 inhibition.2015

    • Author(s)
      Fujie A, Funayama A, Miyauchi Y, Sato Y, Kobayashi T, Kanagawa H, Katsuyama E, Hao W, Tando T, Watanabe R, Morita M, Miyamoto K, Kanaji A, Morioka H, Matsumoto M, Toyama Y and Miyamoto T.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 457 Issue: 3 Pages: 451-456

    • DOI

      10.1016/j.bbrc.2015.01.012

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The Vitamin D Analogue ED71 but Not 1,25(OH)2D3 Targets HIF1α Protein in Osteoclasts.2014

    • Author(s)
      Sato Y, Miyauchi Y, Yoshida S, Morita M, Kobayashi T, Kanagawa H, Katsuyama E, Fujie A, Hao W, Tando T, Watanabe R, Miyamoto K, Morioka H, Matsumoto M, Toyama Y, Miyamoto T.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 11 Pages: e111845-e111845

    • DOI

      10.1371/journal.pone.0111845

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] TNFα promotes osteosarcoma progression by maintaining tumor cells in an undifferentiated state.2013

    • Author(s)
      Mori T
    • Journal Title

      Oncogene

      Volume: Epub ahead of print Issue: 33 Pages: 4236-4241

    • DOI

      10.1038/onc.2013.545

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HIF1α is required for osteoclast activation by estrogen deficiency in postmenopausal osteoporosis.2013

    • Author(s)
      Miyauchi Y, Sato Y, Kobayashi T, Yoshida S, Mori T, Kanagawa H, Katsuyama E, Fujie A, Hao W, Miyamoto K, Tando T, Morioka H, Matsumoto M, Chambon P, Johnson RS, Kato S, Toyama Y, Miyamoto T.
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 110 Issue: 41 Pages: 16568-16573

    • DOI

      10.1073/pnas.1308755110

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] STATs and macrophage fusion.2013

    • Author(s)
      Miyamoto T.
    • Journal Title

      JAKSTAT

      Volume: 2

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of osteoclasts in regulating hematopoietic stem and progenitor cells.2013

    • Author(s)
      Miyamoto T.
    • Journal Title

      World J Orthop.

      Volume: 4 Pages: 198-206

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL-32-PAR2 axis is an innate immunity sensor providing alternative signaling for LPS-TRIF axis.2013

    • Author(s)
      Nakayama M, Niki Y, Kawasaki T, Takeda Y, Ikegami H, Toyama Y, Miyamoto T.
    • Journal Title

      Sci Rep.

      Volume: 3 Issue: 1 Pages: 2960-2960

    • DOI

      10.1038/srep02960

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Twist2 functions as a tumor suppressor in murine osteosarcoma cells.2013

    • Author(s)
      Ishikawa T, Shimizu T, Ueki A, Yamaguchi S, Onishi N, Sugihara E, Kuninaka S, Miyamoto T, Morioka H, Nakayama R, Kobayashi E, Toyama Y, Mabuchi Y, Matsuzaki Y, Yamaguchi R, Miyano S and Saya H
    • Journal Title

      Cancer Sci

      Volume: (in press) Issue: 7 Pages: 880-888

    • DOI

      10.1111/cas.12163

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An essential role for STAT6-STAT1 protein signaling in promoting macrophage cell-cell fusion2012

    • Author(s)
      Miyamoto H, et al.
    • Journal Title

      J Biol Chem.

      Volume: 287 Pages: 32479-84

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Conditional inactivation of Blimp1 in adult mice promotes increased bone mass.2012

    • Author(s)
      Miyauchi Y, Miyamoto H, Yoshida S, Mori T, Kanagawa H, Katsuyama E, Fujie A, Hao W et al.
    • Journal Title

      J Biol Chem

      Volume: 287 Issue: 34 Pages: 28508-28517

    • DOI

      10.1074/jbc.m112.356634

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced susceptibility to lipopolysaccharide-induced arthritis and endotoxin shock in interleukin-32 alpha transgenic mice through induction of tumor necrosis factor alpha2012

    • Author(s)
      Nakayama M., Niki Y., Kawasaki T., Takeda Y., Horiuchi K., Sasaki A., Okada Y., Umezawa K., Ikegami H., Toyama Y. and Miyamoto T.
    • Journal Title

      Arthritis Res Ther

      Volume: 14 Issue: 3

    • DOI

      10.1186/ar3850

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical Significance of Cartilage Biomarkers for Monitoring Structural Joint Damage in Rheumatoid Arthritis Patients Treated with Anti-T NF Therapy2012

    • Author(s)
      Niki Y, et al.
    • Journal Title

      PLoS One

      Volume: 7 Issue: 5 Pages: e37447-e37447

    • DOI

      10.1371/journal.pone.0037447

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PDGFBB promotes PDGFRα-positive cell migration into artificial bone in vivo.2012

    • Author(s)
      Yoshida S, Iwasaki R, Kawana H, Miyauchi Y, Hoshi H, Miyamoto H, Mori T, Kanagawa H et al.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 421 Issue: 4 Pages: 785-789

    • DOI

      10.1016/j.bbrc.2012.04.084

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aldehyde-stress resulting from Aldh2 mutation promotes osteoporosis due to impaired osteoblastogenesis2012

    • Author(s)
      Hoshi H, Hao W, Fujita Y, Funayama A, Miyauchi Y, Hashimoto K, Miyamoto K, (他21名)
    • Journal Title

      J. Bone Miner Res

      Volume: 27(9) Issue: 9 Pages: 2015-2023

    • DOI

      10.1002/jbmr.1634

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serum cartilage metabolites as biomarkers of degenerative lumbar scoliosis2012

    • Author(s)
      Hosogane N, et al
    • Journal Title

      J Orthop Res

      Volume: (In press) Issue: 8 Pages: 1249-53

    • DOI

      10.1002/jor.22067

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] OC-STAMP and DC-STAMP cooperatively modulate cell-cell fusion to form osteoclasts and foreign body giant cells2012

    • Author(s)
      Miyamoto H, et al
    • Journal Title

      J Bone Miner Res

      Volume: (In press) Issue: 6 Pages: 1289-1297

    • DOI

      10.1002/jbmr.1575

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] TNFα and IL-1 promotes osteosarcoma progression by maintaining tumor cells in an undifferentiated state2014

    • Author(s)
      Takeshi Miyamoto
    • Organizer
      Cold Spring Harbor, Asia Bone and Cartilage
    • Place of Presentation
      Suzhou, China
    • Year and Date
      2014-11-03 – 2014-11-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 骨代謝の理解と骨粗鬆症治療2014

    • Author(s)
      宮本健史
    • Organizer
      第16回日本骨粗鬆症学会
    • Place of Presentation
      新宿
    • Year and Date
      2014-10-23 – 2014-10-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 臨床応用を見据えた骨代謝研究2014

    • Author(s)
      宮本健史
    • Organizer
      第29回日本整形外科学会基礎学術総会
    • Place of Presentation
      鹿児島
    • Year and Date
      2014-10-08 – 2014-10-10
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Transcriptional Regulation of Osteoclastogenesis2014

    • Author(s)
      Takeshi Miyamoto
    • Organizer
      5th International Conference on Osteoimmunology
    • Place of Presentation
      Kos, Greece
    • Year and Date
      2014-06-15 – 2014-06-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] RANKLを標的とした新しい骨粗鬆症治療~骨代謝の理解に基づく骨粗鬆症治療~2014

    • Author(s)
      宮本健史
    • Organizer
      第87回日本整形外科学会学術集会
    • Place of Presentation
      神戸
    • Year and Date
      2014-05-22 – 2014-05-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 骨粗鬆症をめぐる最新の基礎研究2014

    • Author(s)
      宮本健史
    • Organizer
      第58回日本リウマチ学会総会・学術集会
    • Place of Presentation
      高輪
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Regulation of haematopoietic stem cells and progenitors by osteoclasts.2013

    • Author(s)
      Miyamoto T
    • Organizer
      1. Annual Meeting of the Japanese Society for Immunology
    • Place of Presentation
      Makuhari
    • Related Report
      2013 Annual Research Report
  • [Presentation] STAT6によるSTAT1の阻害がマクロファージの融合に必須である2013

    • Author(s)
      勝山 詠理、宮本 健史、二木 康夫、戸山 芳昭
    • Organizer
      第28回日本整形外科学会基礎学術集会
    • Place of Presentation
      幕張
    • Related Report
      2013 Annual Research Report
  • [Presentation] 金川裕矢、戸山芳昭、宮本健史2013

    • Author(s)
      ヒトIL-1α conditional transgenicマウスはヒト自己炎症性症候群を反映する
    • Organizer
      第28回日本整形外科学会基礎学術集会
    • Place of Presentation
      幕張
    • Related Report
      2013 Annual Research Report
  • [Presentation] TNFとIL-1は骨肉腫細胞株AXの腫瘍形成に必須のサイトカインである2013

    • Author(s)
      森智章、森岡秀夫、戸山芳昭、宮本健史
    • Organizer
      第28回日本整形外科学会基礎学術集会
    • Place of Presentation
      幕張
    • Related Report
      2013 Annual Research Report
  • [Presentation] 骨恒常性制御の分子機序2013

    • Author(s)
      宮本健史
    • Organizer
      第31回日本骨代謝学会学術総会
    • Place of Presentation
      神戸国際会議場
    • Related Report
      2013 Annual Research Report
  • [Presentation] 整形外科の立場から見たBRONJの病態2012

    • Author(s)
      宮本健史
    • Organizer
      第23回日本臨床口腔病理学会 総会・学術集会
    • Place of Presentation
      東京医科歯科大学(招待講演)
    • Year and Date
      2012-08-30
    • Related Report
      2012 Annual Research Report
  • [Presentation] PDGFBB Promotes PDGFR Alpha-positive Cell Migration into Artificial Bone in vivo2012

    • Author(s)
      Yoshida S, et al.
    • Organizer
      ASBMR Topical Meeting on Bone and Skeletal Muscle Interactions
    • Place of Presentation
      Westein Kansas City at Crown Center
    • Year and Date
      2012-07-16
    • Related Report
      2012 Annual Research Report
  • [Presentation] インターロイキン32aはToll様受容体シグナルを介してサイトカインを誘導し関節炎の病態に関与する2012

    • Author(s)
      中山政憲, 他
    • Organizer
      第27回日本整形外科学会基礎学術集会
    • Place of Presentation
      名古屋国際会議場
    • Related Report
      2012 Annual Research Report
  • [Presentation] in vivoにおいてPDGFBBはPRGFRa陽性細胞の遊走を促進させる2012

    • Author(s)
      吉田重之, 他
    • Organizer
      第57回(公社)日本口腔外科学会総会・学術大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2012 Annual Research Report
  • [Presentation] PDGFBB Promotes PDGFR Alpha-positive Cell Migration into Artificial Bone in vivo2012

    • Author(s)
      Yoshida S, et al.
    • Organizer
      Annual Meeting of the American Society for Bone and Mineral Research 2012
    • Place of Presentation
      Minneapolis Convention Center
    • Related Report
      2012 Annual Research Report
  • [Presentation] ヒト2型糖尿病における骨梁微細構造の解析2012

    • Author(s)
      松崎健一郎, 他
    • Organizer
      第30回日本骨代謝学会学術集会
    • Place of Presentation
      大阪国際会議場
    • Related Report
      2012 Annual Research Report
  • [Presentation] PDGF-BBは人工骨の生体親和性を上昇させる2012

    • Author(s)
      吉田重之, 他
    • Organizer
      第30回日本骨代謝学会学術集会
    • Place of Presentation
      大阪国際会議場
    • Related Report
      2012 Annual Research Report
  • [Presentation] 破骨細胞と骨恒常性制御2012

    • Author(s)
      宮本健史
    • Organizer
      第12回抗加齢医学会総会
    • Place of Presentation
      パシフィコ横浜(招待講演)
    • Related Report
      2012 Annual Research Report
  • [Presentation] RANKLによる新しい破骨細胞の分子機能評価2012

    • Author(s)
      宮本健史
    • Organizer
      第85回日本整形外科学会
    • Place of Presentation
      グランドプリンスホテル京都(招待講演)
    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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